Effect of Hydrophobic Acrylic versus Hydrophilic Acrylic

Intraocular Lens on Posterior Capsule Opacification:

Meta-Analysis
Ying Li1., Jiaxing Wang2., Zhuo Chen1, Xin Tang1*
1 Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Hospital, Tianjin, China, 2 Department of Ophthalmology, Tianjin Medical University General
Hospital, Tianjin, China

Abstract
Purpose: This meta-analysis aims to evaluate the differences in performance of posterior capsular opacification (PCO)
between hydrophobic acrylic intraocular lens (IOLs) and hydrophilic acrylic IOLs.

Setting: Tianjin Medical University, Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Visual Science,
Tianjin, China.

Design: Systematic review of randomized controlled trials (RCTs) or meta-analysis.

Methods: An electronic literature search was performed using the PubMed, EMBASE and Cochrane Library database before
May in 2013 to identify prospective RCTs comparing hydrophobic acrylic IOLs and hydrophilic acrylic IOLs in patients after
phacoemulsification with IOL implantation with a follow-up time of at least 1 year. Pertinent studies were selected by
meeting predefined criteria and reviewed systematically by meta-analysis. The PCO scores and YAG capsulotomy rate, as
indicator of PCO, were measured and discussed in a meta-analysis. Standardized mean differences (SMD), relative risk ratio
(RR), and the pooled estimates were computed according to a random effect model or fixed effect model.

Results: Nine prospective RCTs involving 861 eyes were included in the current meta-analysis. The hydrophobic acrylic IOLs
were favored and the pooled SMD of PCO severity was1.72 (95% confidence interval (CI), 0.20 to 1.23, P = 0.0002) and 1.79
(95% CI, 0.95 to 2.64, P,0.0001) with 1-year follow-up and 2-year follow-up respectively. The pooled RR of Nd:YAG laser
capsulotomy rates at postoperative 2-year follow-up was 6.96 (95% CI, 3.69 to 13.11, P,0.00001) comparing hydrophilic
acrylic IOLs with hydrophobic acrylic IOLs.

Conclusions: Compared with hydrophilic acrylic IOLs, the hydrophobic acrylic IOLs showed superior reduction in rates of
PCO and laser capsulotomy in 2-year follow-up. More RCTs with standard methods for longer follow-up are needed to
validate the association.

Citation: Li Y, Wang J, Chen Z, Tang X (2013) Effect of Hydrophobic Acrylic versus Hydrophilic Acrylic Intraocular Lens on Posterior Capsule Opacification: Meta-
Analysis. PLoS ONE 8(11): e77864. doi:10.1371/journal.pone.0077864
Editor: Helge Bruns, University Hospital Heidelberg, Germany
Received July 11, 2013; Accepted September 13, 2013; Published November 5, 2013
Copyright: ß 2013 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: xtang2013@gmail.com
. These authors contributed equally to this work.

Introduction
With the development of surgical techniques and biomaterial
science, cataract surgery with intraocular lens (IOL) implantation
has brought great benefits for patients. However, posterior capsule
opacification (PCO), remains the most frequent long-term
complication [1], decreasing the visual performance in 1 or 2
years after cataract surgery. Although treatment with Nd:YAG
laser capsulotomy is effective, the complications, such as retina
detachment, macular edema, intraocular pressure elevation [2],
cannot be ignored.
Intraocular lens, with various designs and materials, have been
observed in playing a vital role in the developmentof PCO. Two
areas of concern are the biomaterials and the edge design of IOLs.
Studies have shown that the rate of PCO with sharp edge designed
IOLs was lower due to the inhibition of lens epithelial cells (LECs)
migration [3,4]. Acrylic IOLs with hydrophilic or hydrophobic
surfaces, as two types of biocompatibility materials, safe for
intraocular implantation, have a long history of clinical practice
and have shown significantly lower rates of PCO and less Nd:YAG
laser capsulotomy [5–8]. Studies found that acrylic material has a
relatively low propensity to induce cell proliferation in the capsular
bag [9]. Yet whether the hydrophilic or hydrophobic IOLs are
better for PCO prevention remains controversial.
Numerous studies have compared on PCO to different designs
and materials combinations of IOLs. Few comparative studies,
however have evaluated the differences between hydrophobic
acrylic IOLs and hydrophilic acrylic IOLs with the same edge

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design specifically. The aim of this meta-analysis is to investigate
the differences between hydrophobic and hydrophilic IOLs with
the same edge design in the development of PCO and the rate of
Nd:YAG laser capsulotomy in a 2 year period.
Materials and Methods
Literature Search
This review was conducted following the QUOROM guideline
standards [10]. Reports of randomized controlled trials (RCTs)
comparing hydrophobic acrylic and hydrophilic acrylic IOLs in
patients after phacoemulsification with IOL implantation were
identified through a computerized literature search. The system-
atic search was conducted in the PubMed, EMBASE, and
Cochrane Controlled Trials Register database up to the end of
May 2013 by using the search terms ‘‘posterior capsular opacification’’
‘‘intraocular lens’’ ‘‘hydrophilic’’ ‘‘hydrophobic’’ and limiting the search
to reports of randomized controlled trials. The abstract of all
potentially relevant articles were screened to determine their
relevance followed by evaluation of candidate full articles. In
addition, literature reference proceedings were scanned manually
to obtain extra eligible trials until no more relevant trials were
found in databases. For data collected from duplicate patient
groups, only the most recent studies were included in each part of
meta-analysis. The process of trials selection is shown in Figure 1.
Two independent investigators performed the literature search
(YL, JXW).
Selection Criteria
Selected trials fulfilling the following inclusion criteria were used
in this analysis: (1) prospective design, randomized controlled trial;
(2) population, patients with senile cataract undergoing cataract
surgery; (3) intervention, phacoemulsification and IOL implanta-
tion; (4) comparison, hydrophobic acrylic and hydrophilic acrylic
IOLs; all involved IOLs are designed with sharp edge;(5) outcome
variables, at least one of the following primary outcome variables:
PCO score, Nd:YAG capsulotomy rate.
Figure 1. Flow chart of literature search and study selection.
doi:10.1371/journal.pone.0077864.g001
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Posterior Capsule Opacification: Meta-Analysis
Exclusion criteria were as follows: (1) patients with a history of
ocular diseases other than senile cataract; (2) patients with a history
of intraocular surgery other than IOL; (3) Cases with intraoper-
ative complications, such as incomplete continuous curvilinear
capsulorhexis (CCC), posterior capsule rupture or whose with
postoperative complications (eg, iris synechia); (4) follow-up time of
less than one year.
Data Extraction and Quality Assessment
Two reviewers (YL, JXW) completed searches independently
according to the above the criteria, assessed the methodological
quality of trials and extracted data from each eligible randomized
clinical trial results. Differences were resolved by discussion to
reach consensus between the investigators and results were
checked by the third author (ZC) when required. The following
items were collected from each trial: author’s name, year of
publication, design of study, patients’ mean age, gender, group
size, IOL biomaterials and special designs, evaluation of PCO, and
Nd:YAG capsulotomy (number or rate), follow-up period,
respectively.
Outcome Measures
The primary outcome measure was the difference in PCO
intensity or PCO score from software between the 2 types of IOLs
at 1-year and 2-year follow-up post-operation. The secondary
outcome measures were Nd:YAG capsulotomy rate at 2-year
follow-up post-operation. For those patients who underwent
Nd:YAG capsulotomy, the PCO value just before Nd:YAG
capsulotomy was used for further statistical analysis. If there was
more than 1 published report on the same population or group of
patients, the most recent results with complementary data from
previous articles were used for statistical analysis.
Statistical Analysis and Assessment of Heterogeneity
According to various measurement scales, PCO severity
outcomes, as continuous data, were pooled using standardized
mean differences (SMD) with 95% confidence intervals (CIs)[11].
The data of Nd:YAG capsulotomy rate, as dichotomous data,
2 November 2013 | Volume 8 | Issue 11 | e77864
 Posterior Capsule Opacification: Meta-Analysis

were tabulated into 262 tables and the relative risk ratio (RR) and Table 1. Evaluation of the quality of RCTs included in the
95% CIs of the results were compared. Heterogeneity was also meta-analysis.
assessed through chisquare test, and an I2 value greater than 50%,
P,0.1 was considered significant. We evaluated the pooled
summary effect by using random-effect model. Otherwise(I2 Jadad
value#50%, P$0.1), data were combined using fixed-effect model Study Random Blind Withdraw score(0–5)
to reduce the heterogeneity between studies. Finally, publication
Gangwani 2011 Appropriate Double-blind Described 5
bias was assessed visually with funnel plots. The statistical analyses
were carried out with RevMan software (version 5.0, The Iwase 2011 Yes Yes Described 3
Cochrane Collaboration). Vasavada 2011 Appropriate Yes Described 4
Kang 2009 Yes Yes Described 3
Results Cleary 2009 Appropriate Yes Described 4
Kugelberg 2008 Appropriate Yes Described 4
Study included
Hancox 2007 Yes Yes Described 3
The results of our research strategy are shown in Fig. 1. A total
of 132 potentially relevant publications were identified through the Kugelberg 2006 Appropriate Yes Described 4
literature search from multiple databases before May in 2013, 20 Heatley 2005 Yes Yes Described 3
of which were based on their titles and abstracts. Only 9 random
controlled trials [2,8,12–18] were eligible for this meta-analysis. doi:10.1371/journal.pone.0077864.t001

Quality assessment of eligible studies and characteristics
of included IOL
The methodological quality of trials that were identified and the
characteristics of 9 potential RCTs included in the current meta-
analysis are presented in Table 1. In these 9 RCTs included in this
meta-analysis, the investigators described the random component
in a sequence generation process such as: using an envelope
[2,12,17], or referring to a computer random number genera-
tor[14,15]. Only 1 of 9 studies used double-blinding12, while the
others used single-blinding[2,8,13–18]. Recruited RCTs were
carried out in many countries including United Kingdom, Japan,
India, Sweden and Korea. The length of the studies was between 1
and 2 years. All studies included described the dropout patients’
number and reasons respectively. Characteristics of IOLs included
in the recruited studies are presented in Table 2.
Efficacy analysis
Effects of hydrophobic acrylic versus hydrophilic acrylic
IOLs on development of posterior capsule opacification in
1-year follow-up. Based on 7 studies (620 total eyes) that
evaluated PCO after a 1-year follow-up period[2,8,12,14–16,18],
hydrophobic acrylic IOLs were associated with significantly lower
PCO scores than hydrophilic acrylic IOLs; the SMD was 1.72
(95% CI, 0.82 to 2.63, P = 0.0002). The data showed that they had
heterogeneity of effect size (P,0.00001, I2 = 96%), so the random
effect model was used for meta-analysis. The results are shown in
Figure 2.
Effects of hydrophobic acrylic versus hydrophilic acrylic
IOLs on development of posterior capsule opacification in
2-year follow-up. Seven studies involving 525 eyes used
different scales to report the outcomes for PCO after 2-year
follow-up [8,12–14,16–18]. They also had heterogeneity of effect
size (P,0.00001, I2 = 94%), so the random effect model was used
for meta-analysis. A significant difference was found between the
hydrophobic acrylic and hydrophilic acrylic IOLs; the SMD was
1.79 (95% CI, 0.95 to 2.64, P,0.0001), indicating that hydro-
phobic acrylic IOLs were associated with lower PCO score in 2-
year follow-up. The results are shown in Figure 3.
Effects of hydrophobic acrylic versus hydrophilic acrylic
IOLs on rate of Nd:YAG capsulotomy in 2-year follow-
up. Seven studies[8,12–14,16–18] involving 546 eyes compared
the Nd:YAG capsulotomy rate of hydrophobic acrylic IOLs with
hydrophilic acrylic IOLs in a 2-year follow-up period. No
statistical heterogeneity was detected between studies (P = 0.85,
I2 = 0%). Therefore, the fixed effect model was analyzed for this
research. The results from analysis suggest that hydrophobic
acrylic IOLs had a lower Nd:YAG capsulotomy rate; the RR was
6.96(95% CI, 3.69 to 13.13, P,0.00001). The results are shown in
Figure 4.
Publication Bias
The publication bias was assessed graphically for each outcome
independently using funnel plots. The funnel shaped with the apex
near the symmetry, which suggesting publication bias is less of a
concern.
Discussion
At present, PCO remains the most common complication of
modern cataract surgery. There is considerable interest in the
impact of IOL on the development of PCO since characteristics
and designs of IOLs play a crucial role in preventing PCO.
Furthermore, differences in PCO performance between IOLs
were likely to reflect their distinction in biomaterials and designs.
Both hydrophilic and hydrophobic have been commonly used in
cataract surgeries. Hydrophobic acrylic IOLs have a long track
record of good PCO rate [19]. However, due to the mechanical
properties, hydrophilic acrylic IOLs may be more suitable for
implantation through smaller IOL injection systems [12]. Addi-
tionally they may have superior biocompatibility and less
macrophage adhesion especially when a blood-aqueous barrier
breakdown has occurred, such as those with glaucoma, uveitis, and
diabetes mellitus [20]. Although higher PCO rates have been
reported for hydrophilic materials [2,17,21], controversy remains
over whether this finding is a result of differences in material
properties or variation in the optic edge design [22]. The potential
mechanism that IOLs with sharp optic edge prevent PCO,
including cell migration prevention [23], pressure atrophy [15]
and contact inhibition [24], have gained acceptance widely. The
PCO rate in hydrophilic acrylic IOLs implantation, which have an
improved 360-degree sharp edge, is reported lower than with older
hydrophilic models [25,26]. It should not be ignored that many
studies have a significant limitation, comparing hydrophilic IOLs
with round optic edges and hydrophobic IOLs with sharp optic
edges [8,27,28].
Since complete surgical removal lens epithelial cells (LECs) is
not possible with modern surgical technology, the migration of
remaining equatorial LECs which form PCO may be difficult to

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 Table 2. Characteristics of IOLs included in the meta-analysis.

PCO
Sharp Edge Haptic evaluation
IOLs Optic Material Haptic Material Lens Type Optic Diameter Design Optic Shape Angulation Distinctive Feature system

Acrysof SA60AT Hydrophobic Acrylic Acrylic 1-piece 6 mm Posterior Anterior Asymmetric 0 N/A AQUA
biconvex Scheimpflug
POCOman

PLOS ONE | www.plosone.org

Acrysof SN60WF Hydrophobic Acrylic Acrylic 1-piece 6 mm Posterior Posterior biconvex 0 N/A EPCO
Sensar AR40e Hydrophobic Acrylic PMMA 3-piece 6 mm Posterior Equal biconvex 5 N/A POCOman
Acrysof MA60AC Hydrophobic Acrylic PMMA 3-piece 6 mm Posterior Anterior Asymmetric 10 N/A POCOman
Biconvex
Acrysof MA30AC Hydrophobic Acrylic PMMA 3-piece 5.5 mm Double Anterior Asymmetric 5 N/A POCOman
Biconvex
Idea 613XC Hydrophilic Acrylic Acrylic 1-piece 6 mm Double Biconvex 9 Broad optic-haptic junction AQUA
Meridian HP60M Hydrophilic Acrylic PMMA 1-piece 6 mm Double Anterior biconvex 6 N/A Scheimpflug
C-flex 570C Hydrophilic Acrylic Acrylic 1-piece 5.75 mm Double N/A 0 N/A EPCO
Akreos Adapt Hydrophilic Acrylic Acrylic 1-piece 6 mm Double Equal biconvex 0 N/A EPCO
Bio Vue3 Hydrophilic Acrylic PVDF+ 3-piece 6 mm Double Equal biconvex 5 Heparin surface modification POCOman
MC611M Hydrophilic Acrylic Acrylic 1-piece 6 mm Double N/A 0 Broad optic-haptic junction POCOman
BL27 Hydrophilic Acrylic Acrylic 1-piece 6 mm Posterior N/A 0 N/A POCOman

4
1CU Hydrophilic Acrylic Acrylic 1-piece 5.5 mm Double Equal biconvex 0 4 haptics Accommodation POCOman
Centerflex 570H Hydrophilic Acrylic Acrylic 1-piece 5.75 mm Posterior Equal biconvex 0 N/A POCOman

doi:10.1371/journal.pone.0077864.t002
Posterior Capsule Opacification: Meta-Analysis

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 Posterior Capsule Opacification: Meta-Analysis

Figure 2. Forest plots describing effects of hydrophobic acrylic versus hydrophilic acrylic IOLs on development of posterior capsule
opacification in 1-year follow-up. (Chi2 = chi square statistic, CI = confidence interval, df = degrees of freedom, I2 = I-square heterogeneity
statistic, IV = inverse variance, SMD = standard mean difference, Z = Z-statistic).
doi:10.1371/journal.pone.0077864.g002

avoid. As a proliferative pathological process, there is a close
relationship between the severity of PCO and post-operative
follow-up time. The longer follow-up period, the better clinicians
understand the effect of IOLs on the development of PCO. Some
studies have shown no differences in PCO rates between the two
different materials IOLs after cataract surgery 1 year [13,15].
Others have shown significantly different results [14,16]. Indeed,
some researches have addressed the influence of various IOLs on
the incidence of PCO in different lengths of follow-up [1,29].
Therefore long term randomized controlled trials, especially with a
multi center large sample size, are needed to evaluate further
effects of various IOL biomaterials with similar optic edge designs
in decreasing PCO and Nd:YAG capsulotomy rates.
This meta analysis evaluated the 1-year and 2-year postoper-
ative PCO results and rate of Nd:YAG laser capsulotomy in 2-year
follow-up between hydrophilic acrylic and hydrophobic acrylic
IOLs implantation respectively. All the IOLs involved in this
analysis were designed to prevent PCO by incorporating a sharp
edge. Therefore, the differences shown in this analysis may be
interpreted primarily based on material effects. The result of this
meta-analysis support the theory that compared to hydrophilic
acrylic IOLs, hydrophobic acrylic IOLs led to significantly less
PCO in 1-year and 2-year follow-up periods. Meanwhile, the rates
of Nd:YAG laser capsulotomy were also reduced following
hydrophobic acrylic IOLs implantation 2-year post-operation. A
reasonable interpretation for the difference in this meta-analysis
may be that hydrophobic acrylic IOLs can adhere to collagen
membrane [30], leading to tight apposition of IOLs in posterior
capsular bag, and advanced adhesiveness through fibronectin [8].
This may result in less space between IOLs and posterior capsule
where the LECs could migrate. On the other hand, the
hydrophilic surface properties were found to promote proliferation
and migration of LECs from the equatorial area to the visual
region [31]. Moreover, studies compared electron microscope
images and found the edge of hydrophilic IOLs to be less sharp
than hydrophobic IOLs at several optical powers [13]. The
potential reason could be hydrophilic acrylic IOLs are machined
in the dehydrated state and then rehydrated, which can lead to loss
of edge sharpness [32]. These differences in manufacturing
techniques may explain why hydrophobic IOLs appear to have
relatively better PCO performance. The recent study [33] suggest
a new aspect to consider in lens material, hybrid technique
(hydrophilic center and hydrophobic surface coated IOLs),
indicating that hybrid IOLs are less susceptible than hydrophilic
IOLs to cell adhesion and less susceptible than hydrophobic IOLs
to glistening formation. The copolymer hybrid IOLs may present
certain important advantages and should therefore be further
evaluated with PCO performance in clinical studies.
The studies in this meta-analysis used a variety of different
evaluation systems for PCO analysis, such as Scheimpflug
photography system [13], POCOman system [2,8,15–18], AQUA
(Automated Quantification of After-Cataract system) 12, and
EPCO (Evaluation of Posterior Capsule Opacification software)
[14]. Each of these software systems has particular features that
made them vulnerable. POCOman and AQUA system are
objective, however, they do not incorporate whether PCO is
peripheral or central location and show limited points [29]. EPCO
evaluates the construct validity [34], but it is a subjective style. On
account of the different analysis systems for PCO across the
studies, SMDs were used in this meta-analysis as in previous
studies [29].

Figure 3. Forest plots describing effects of hydrophobic acrylic versus hydrophilic acrylic IOLs on development of posterior capsule
opacification in 2-year follow-up. (Chi2 = chi square statistic, CI = confidence interval, df = degrees of freedom, I2 = I-square heterogeneity
statistic, IV = inverse variance, SMD = standard mean difference, Z = Z-statistic).
doi:10.1371/journal.pone.0077864.g003

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Figure 4. Forest plots describing Effects of hydrophobic acrylic versus hydrophilic acrylic IOLs on rate of Nd:YA Gcapsulotomy in 2-
year follow-up. (Chi2 = chi square statistic, CI = confidence interval, df = degrees of freedom, I2 = I-square heterogeneity statistic, IV = inverse
variance, RR = risk ratio, Z = Z-statistic).
doi:10.1371/journal.pone.0077864.g004
Limitation of this meta-analysis may be found. First, even
though all the IOLs in this meta-analysis were designed with sharp
edge, as a key factor in retarding PCO, there were various extra
factor could make an impact. For example, the IOLs with broad
optic-haptic junctions [16], the heparin-surface-modified [15], the
asphericity on the posterior surface [35], the degree of haptic
angulation [36], and optic size [37] appear to exert influence upon
PCO formation. The pathophysiology of PCO is multifactorial.
Since dissociation of each factor in PCO development is almost
impossible, it is very difficult to observe individual elements in
clinical practice. Second, although we conducted a thorough
electronic search and a manual search of the references of relevant
results to minimize selection and publication bias, there were not
sufficient studies included to verify if asymmetry exists in a funnel
plot. Consequently, long-term postoperative follow-up of multi-
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Supporting Information
Checklist S1 PRISMA 2009 Checklist.
(DOC)
Prisma Flow Diagram S1 PRISMA 2009 Flow Diagram.
(DOC)
Author Contributions
Conceived and designed the experiments: YL ZC XT. Performed the
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7 November 2013 | Volume 8 | Issue 11 | e77864